Computer-assisted multistep chemoenzymatic retrosynthesis using a chemical synthesis planner
Name
d3sc01355c.pdf
Description
Published version
Size
1.28 MB
Format
Adobe PDF
Checksum (MD5)
e4b00afb8bd64e1743b712834093e548
Author(s)
Sankaranarayanan, Karthik
Jensen, Klavs F
Date Issued
2023
Journal
Chemical Science
Publisher
Royal Society of Chemistry
Citation
Chem. Sci., 2023,14, 6467-6475
Version
Final published version
Abstract
Chemoenzymatic synthesis methods use organic and enzyme chemistry to synthesize a desired small molecule. Complementing organic synthesis with enzyme-catalyzed selective transformations under mild conditions enables more sustainable and synthetically efficient chemical manufacturing. Here, we present a multistep retrosynthesis search algorithm to facilitate chemoenzymatic synthesis of pharmaceutical compounds, specialty chemicals, commodity chemicals, and monomers. First, we employ the synthesis planner ASKCOS to plan multistep syntheses starting from commercially available materials. Then, we identify transformations that can be catalyzed by enzymes using a small database of biocatalytic reaction rules previously curated for RetroBioCat, a computer-aided synthesis planning tool for biocatalytic cascades. Enzymatic suggestions captured by the approach include ones capable of reducing the number of synthetic steps. We successfully plan chemoenzymatic routes for active pharmaceutical ingredients or their intermediates (e.g., Sitagliptin, Rivastigmine, and Ephedrine), commodity chemicals (e.g., acrylamide and glycolic acid), and specialty chemicals (e.g., S-Metalochlor and Vanillin), in a retrospective fashion. In addition to recovering published routes, the algorithm proposes many sensible alternative pathways. Our approach provides a chemoenzymatic synthesis planning strategy by identifying synthetic transformations that could be candidates for enzyme catalysis.
MIT Department
Massachusetts Institute of Technology. Department of Chemical Engineering
Terms of Use
Creative Commons Attribution-Noncommercial
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1039/d3sc01355c
